The goal of these studies is to characterize the nature or resistance to chemotherapeutic drugs of human mammary carcinomas in culture. To do this, we will utilize some new techniques that we have developed that allow us to readily isolate, cryopreserve and culture both normal and malignant human mammary epithelium. The cells can be grown in a highly efficient clonogenic assay suitable for quantitating response to various drugs. We will determine whether there are differences in sensitivity among specimens and whether there is heterogeneity within a single specimen. We will also determine whether tumors behave differently than nonmalignant tissue and whether there are differences in sensitivity related to patient history or age. We will begin to evaluate mechanisms for any differences that we observe by measuring uptake of radioactive drugs. The drugs that we will study are those commonly used to treat breast cancer and include adriamycin (preliminary data suggests that there are differences in sensitivity among specimens), methotrexate, fluorouracil, vincristine, vinblastine, mitomycin, L-phenylalanine mustard, and cytoxan.